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CAS 1256580-46-7

Chemistry

Chemistry

MARKET PLACE

1 APIs

1 APIs

Also known as: 1256580-46-7, Ch5424802, Alecensa, Af-802, Ch 5424802, Af802

Molecular Formula

C₃₀H₃₄N₄O₂

Molecular Weight

482.6 g/mol

InChI Key

KDGFLJKFZUIJMX-UHFFFAOYSA-N

FDA UNII

LIJ4CT1Z3Y

Alectinib is an orally available inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK) with antineoplastic activity. Upon administration, alectinib binds to and inhibits ALK kinase, ALK fusion proteins as well as the gatekeeper mutation ALKL1196M known as one of the mechanisms of acquired resistance to small-molecule kinase inhibitors. The inhibition leads to disruption of ALK-mediated signaling and eventually inhibits tumor cell growth in ALK-overexpressing tumor cells. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development. ALK dysregulation and gene rearrangements are associated with a series of tumors.

Alectinib is a Kinase Inhibitor. The mechanism of action of alectinib is as a Kinase Inhibitor.

1 2D Structure

CAS 1256580-46-7

2 Identification

2.1 Computed Descriptors

2.1.1 IUPAC Name

9-ethyl-6,6-dimethyl-8-(4-morpholin-4-ylpiperidin-1-yl)-11-oxo-5H-benzo[b]carbazole-3-carbonitrile

2.1.2 InChI

InChI=1S/C30H34N4O2/c1-4-20-16-23-24(17-26(20)34-9-7-21(8-10-34)33-11-13-36-14-12-33)30(2,3)29-27(28(23)35)22-6-5-19(18-31)15-25(22)32-29/h5-6,15-17,21,32H,4,7-14H2,1-3H3

2.1.3 InChI Key

KDGFLJKFZUIJMX-UHFFFAOYSA-N

2.1.4 Canonical SMILES

CCC1=CC2=C(C=C1N3CCC(CC3)N4CCOCC4)C(C5=C(C2=O)C6=C(N5)C=C(C=C6)C#N)(C)C

2.2 Other Identifiers

2.2.1 UNII

LIJ4CT1Z3Y

2.3 Synonyms

2.3.1 MeSH Synonyms

1. Alecensa

2. Ch5424802

3. Ro5424802

2.3.2 Depositor-Supplied Synonyms

1. 1256580-46-7

2. Ch5424802

3. Alecensa

4. Af-802

5. Ch 5424802

6. Af802

7. Ro5424802

8. Alectinib (ch5424802)

9. Unii-lij4ct1z3y

10. 9-ethyl-6,6-dimethyl-8-(4-morpholinopiperidin-1-yl)-11-oxo-6,11-dihydro-5h-benzo[b]carbazole-3-carbonitrile

11. Ch-5424802

12. 9-ethyl-6,6-dimethyl-8-(4-morpholin-4-ylpiperidin-1-yl)-11-oxo-5h-benzo[b]carbazole-3-carbonitrile

13. Af 802

14. Lij4ct1z3y

15. 9-ethyl-6,11-dihydro-6,6-dimethyl-8-[4-(4-morpholinyl)-1-piperidinyl]-11-oxo-5h-benzo[b]carbazole-3-carbonitrile

16. Chembl1738797

17. Ro-5424802

18. Arq-761

19. 9-ethyl-6,6-dimethyl-8-[4-(morpholin-4-yl)piperidin-1-yl]-11-oxo-6,11-dihydro-5h-benzo[b]carbazole-3-carbonitrile

20. 9-ethyl-6,6-dimethyl-8-[4-(morpholin-4-yl)piperidin-1-yl]-11-oxo-5h-benzo[b]carbazole-3-carbonitrile

21. Alectinib [inn]

22. 9-ethyl-6,11-dihydro-6,6-dimethyl-8-(4-(4-morpholinyl)-1-piperidinyl)-11-oxo-5h-benzo(b)carbazole-3-carbonitrile

23. Alectinib [usan:inn]

24. 5h-benzo(b)carbazole-3-carbonitrile, 9-ethyl-6,11-dihydro-6,6-dimethyl-8-(4-(4-morpholinyl)-1-piperidinyl)-11-oxo-

25. 5h-benzo[b]carbazole-3-carbonitrile, 9-ethyl-6,11-dihydro-6,6-dimethyl-8-[4-(4-morpholinyl)-1-piperidinyl]-11-oxo-

26. 9-ethyl-6,6-dimethyl-8-(4-(morpholin-4-yl)piperidin-1-yl)-11-oxo-6,11-dihydro-5h-benzo(b)carbazole-3-carbonitrile

27. Alectinib Free Base

28. Emh

29. Alectinib [mi]

30. Alectinib (usan/inn)

31. Alectinib [usan]

32. Alectinib [who-dd]

33. Ch5424802(alectinib)

34. Ch 5424802, Alectinib

35. Mls006010971

36. Schembl896753

37. Gtpl7739

38. Chebi:90936

39. Amy3288

40. Dtxsid50154840

41. Ex-a406

42. Ch-5424802 Hcl

43. Hms3672c13

44. Hms3744i17

45. Bcp02589

46. Bdbm50362781

47. Mfcd19440988

48. Nsc764040

49. Nsc764821

50. Nsc794611

51. Nsc799328

52. S2762

53. Zinc66166864

54. 1256580-46-7 (free Base)

55. Akos025290737

56. Bcp9000514

57. Cs-0518

58. Db11363

59. Nsc-764040

60. Nsc-764821

61. Nsc-794611

62. Nsc-799328

63. Rg-7853

64. Sb16515

65. Ncgc00346688-01

66. Ncgc00346688-03

67. Ncgc00346688-04

68. 9-ethyl-6,11-dihydro-6,6-dimethyl-8-[4-(4-morpholinyl)-1-piperidinyl]-11-oxo-5h-benzo[b]carbazole-3-

69. Ac-29020

70. As-17008

71. Hy-13011

72. Smr004702775

73. A8393

74. Ft-0748626

75. Ch-5424802/rg-7853

76. D10542

77. J-005256

78. J-519506

79. Q21099132

80. Ch5424802,cas:1256580-46-7

81. 9-ethyl-6,11-dihydro-6,6-dimethyl-8-[4-(4-morpholinyl)-1-piperidinyl]-11-oxo-5h-benzo[b]carbazole-3-carbonitrilech5424802

82. 9-ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5h-benzo[b]carbazole-3-carbonitrile

83. 9-ethyl-6,6-dimethyl-8-(4-morpholin-4-ylpiperidin-1-yl)-11-oxo-5h-benzo[b]carbazol-3-carbonitril

2.4 Create Date

2010-12-27

3 Chemical and Physical Properties

Molecular Formula	C₃₀H₃₄N₄O₂
Molecular Weight	482.6 g/mol
XLogP3	5.2
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	3
Exact Mass	482.26817634 g/mol
Monoisotopic Mass	482.26817634 g/mol
Topological Polar Surface Area	72.4 Å²
Heavy Atom Count	36
Formal Charge	0
Complexity	867
Isotope Atom Count	0
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Covalently Bonded Unit Count	1

4 Drug and Medication Information

4.1 Drug Information

1 of 1
Drug Name	ALECENSA
Active Ingredient	ALECTINIB HYDROCHLORIDE
Company	HOFFMANN-LA ROCHE (Application Number: N208434. Patents: 9126931, 9365514, 9440922)

4.2 Drug Indication

Alectinib is a kinase inhibitor indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

FDA Label

Alecensa as monotherapy is indicated for the first-line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC).

Alecensa as monotherapy is indicated for the treatment of adult patients with ALKpositive advanced NSCLC previously treated with crizotinib.

5 Pharmacology and Biochemistry

5.1 FDA Pharmacological Classification

5.1.1 Active Moiety

ALECTINIB

5.1.2 FDA UNII

LIJ4CT1Z3Y

5.1.3 Pharmacological Classes

Mechanisms of Action [MoA] - Kinase Inhibitors

5.2 ATC Code

L01ED03

L01XE36

S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355

L - Antineoplastic and immunomodulating agents

L01 - Antineoplastic agents

L01E - Protein kinase inhibitors

L01ED - Anaplastic lymphoma kinase (alk) inhibitors

L01ED03 - Alectinib

5.3 Absorption, Distribution and Excretion

Absorption

Alectinib reached maximal concentrations at 4 hours following administration of 600 mg twice daily under fed conditions in patients with ALK-positive NSCLC. The absolute bioavailability was 37% in the fed state. A high-fat, high-calorie meal increased the combined exposure of alectinib and its major metabolite M4 by 3.1-fold following oral administration of a single 600 mg dose.

Route of Elimination

When radioactively labeled, 98% of radioactivity was found in feces with 84% of that amount excreted as unchanged alectinib and 6% as M4. Less than 0.5% was found to be recovered in urine.

Volume of Distribution

4016 L

Clearance

The apparent clearance is 81.9L/hr for alectinib and 217 L/hr for M4.

5.4 Metabolism/Metabolites

Alectinib is metabolized by CYP3A4 to its major active metabolite M4. M4 is then further metabolized by CYP3A4. Both alectinib and M4 demonstrate similar in vivo and in vitro activity. In vitro studies suggest that alectinib is not a substrate for P-gp while M4 is.

5.5 Biological Half-Life

The mean elimination half life is 33 hr for alectinib and 31 hr for M4.

5.6 Mechanism of Action

Alectinib is a second generation oral drug that selectively inhibits the activity of anaplastic lymphoma kinase (ALK) tyrosine kinase. It is specifically used in the treatment of non-small cell lung cancer (NSCLC) expressing the ALK-EML4 (echinoderm microtubule-associated protein-like 4) fusion protein that causes proliferation of NSCLC cells. Inhibition of ALK prevents phosphorylation and subsequent downstream activation of STAT3 and AKT resulting in reduced tumour cell viability. Both alectinib and its major active metabolite M4 demonstrate similar in vivo and in vitro activity against multiple mutant forms of ALK.